hematology

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HEMATOLOGY AND ENDOCRINE
BY
Dr. Rasha Ibrahim Ibrahim
Assistant Professor Internal Medicine-Hematology Department

3. Effect of Endocrine System on Hematopoiesis.
Hematological Manifestations of Endocrine Disorders.
Endocrine Manifestations of Hematological Disorders.
Endocrine Complications Associated with Treatments of
Hematological Diseases.
Disorders that Presented by Both Hematological
and Endocrine Manifestations.

7. Effect of Endocrine System on Normal Hematopoiesis.
Hematological Manifestations of Endocrine Disorders.
Endocrine Manifestations of Hematological Disorders.
Endocrine Complications Associated with Treatments of
Hematological Diseases.
Disorders that Presented by Both Hematological
and Endocrine Manifestations.

8. • Anemia may be the first recognized manifestation of
an endocrine disorder.
• Anemia resulting from endocrine disease generally is
mild to moderate

10. Pituitary Insufficiency
• Hypopituitarism results in a moderate normochromic normocytic Anemia,
with an average hemoglobin of 10 g/dl .
• the anemia of hypopituitarism results from the absence of the anterior lobe
hormones, although the exact role of each of these hormones in the
pathogenesis of anemia is unknown.
• Red cell survival is normal in hypopituitarism, but the marrow is hypo-
plastic.
• In addition to anemia, Leukopenia and even Pancytopenia can occur.
• Replacement therapy with a combination of thyroid, adrenal, and gonadal
hormones usually effectively corrects anemia and other cytopenias.

12. Hypothyroidism
• The Anemia usually is mild to moderate, with hemoglobin concentrations
rarely less than 8 g/dl .
• A concomitant decrease in plasma volume makes the hemoglobin
concentration an unreliable indicator of the red cell mass.
• The associated anemia has been described variably as normocytic,
macrocytic, or microcytic.
• Hypothyroidism may contribute to the development of iron deficiency as
a result of increased predisposition to menorrhagia.
• Males with hypothyroidism may be iron deficient, possibly because of an
associated achlorhydria or because thyroid hormone augments iron
absorption.

13. • Macrocytosis usually result from accompanying B12 or folate
deficiency.
• An association between hypothyroidism and pernicious anemia
is established.
• When these confounding causes of anemia are excluded, it is
evident that anemia also is a direct consequence of thyroid
hormone deficiency.

14. • The response to thyroid hormone therapy is gradual. Slow
improvement in hemoglobin is seen over a several-month
period.
• White blood cell and platelet counts usually are unaffected .
• However, Pancytopenia in association with marrow hypoplasia
has been reported in a patient with myxedema coma.

15. Hyperthyroidism
• Although thyroid hormone administration increases red cell
production in animals, humans with hyperthyroidism generally do
not have polycythemia.
• Anemia is present in 10 to 25 percent of these patients.
• This finding may be the result of increased plasma volume;
however, decreased red cell survival and ineffective erythropoiesis
also have been described in patients with hyperthyroidism.
• A patient with autoimmune hemolytic anemia and
hyperthyroidism has been described.

17. Adrenal Insufficiency
• A normocytic normochromic Anemia may be seen in primary adrenal
insufficiency (Addison disease), but the anemia may be masked by the
concomitant reduction in plasma volume that is common in this disease
• Pernicious anemia occurs in patients with autoimmune adrenal
insufficiency but is seen primarily in patients with type I polyglandular
autoimmune syndrome.

18. Pheochromocytomas
• Are rarely associated with Polycythemia. This finding is believed to be
the result of autonomous erythropoietin production by the tumor, often
mediated by von Hippel-Lindau mutations that cause or contribute to
pheochromocytoma development
Cushing syndrome &primary aldosteronism
• May be associated with Polycythemia

20. Hyperparathyroidism
• Anemia is present in 3 to 5 % of patients with primary
hyperparathyroidism.
• The anemia is normochromic and normocytic and resolves or
improves after parathyroidectomy.
• The cause of the anemia is unknown; marrow fibrosis has been
described in a few patients.

22. • Diabetes mellitus (DM) is a metabolic disorder of great impact
worldwide.
• Many hematologic abnormalities have been defined in diabetic
patients but there are no classical hematological findings.
• DM is accompanied by mild-to-moderate Anemia, often
called anemia of chronic disease

23. • Patients with diabetes and nephropathy were twice as likely to
have anemia compared to those with similar degree of renal
impairment from other causes.
• There is an increasing number of diabetic patients without renal
impairment who are anaemic.

24. Various hypotheses have been proposed
• Chronic renal hypoxia
• Symptomatic autonomic neuropathy causing efferent denervation of the
kidney
• Loss of appropriate (EPO) production
• Hyperglycemia may lead to shortened red cell life span and decreased
erythrocyte deformability
• Systemic inflammation Increasing proinflammatory cytokines,especially
IL-6, antierythropoietic also promotes apoptosis of immature erythrocytes .
• Drugs as use of metformin that may causes pancytopenia, megaloblastic
anemia

25. • Anemia in diabetic person has a significant adverse effect on quality of
life and is associated with disease progression and the development of
comorbidities.
• Anemia can falsely lead to low HbA1c levels which may result in under
treatment of hyperglycemia which in turn will contribute to the
progression of both micro and macro vascular complications.
• The regular screening for anemia can help slow the progression of
vascular complications in these patients.

26. • Abnormalities of leukocyte functions like defects in
adherence, phagocytosis, random migration, chemotaxis are also
described.
• Patients with diabetes are more prone for recurrent infections.

27. • Abnormal platelet function increased platelet aggregability,
Platelet hyperactivity, accelerated platelet turnover and giant
platelets with increased MPV has been observed leading to
thrombotic predisposition
• This is correlated with degree of hyperglycemia and poor control
of DM and is associated with cardiovascular complications

29. Function of the Thymus
• In ancient times, the thymus was believed to be the seat of the
soul or the organ of purification of the nervous system .Later, the
thymus was thought to be a protective thoracic cushion .
• The thymus is one of the central lymphoid organs and plays an
important role in cellular immunity as it serve as the site of T-
cell differentiation and maturation .

30. • Pure red cell aplasia occurs in 5% of
thymoma patients, whereas thymomas are
found in 50% of patients with pure red
cell aplasia .
• Hypogammaglobulinemia 10% of the
patients with adult-onset
hypogammaglobulinemia have a
thymoma, and among patients with a
thymoma, 5% will have
hypogammaglobulinemia
• Hemolytic anemia
• Acute leukemia
• Multiple myeloma
• Lymphoma
• Pancytopenia
Medical Conditions Associated with Thymic Disease
A variety of pathologic conditions are known to be associated with thymic
lesions.
Myasthenia gravis is the most common and has the most well established
association with thymoma.
Main Hematologic disorders associated with Thymic disorders

31. Effect of Endocrine System on Normal Hematopoiesis.
Hematological Manifestations of Endocrine Disorders.
Endocrine Manifestations of Hematological Disorders.
Endocrine Complications Associated with Treatments of
Hematological Diseases.
Disorders that Presented by Both Hematological
and Endocrine Manifestations.

33. • Regular transfusion in thalassemia major increases life expectancy and
improves quality of life, but results in iron overload, which had toxic
effects to organs including endocrine glands.
• The introduction of iron chelation therapy has reduced its toxicity, but
complications may still occur.
• In Egypt, most of our patients did not receive optimal iron chelation
therapy, which might result in higher prevalence of endocrine
complications.

34. Girls
-menarche is delayed
-breast development is poor
-patients are frequently
oligomenorrheic
Or amenorrheic
Boys
-no or sparce facial and body hair
-tend to have decreased libido
Endocrine and metabolic abnormalities
• Hypogonadism 40-55%
• Growth failure 33%
Growth retardation that happen due to anemia ,hypertransfusion frequently restores
growth rate to normal.

35. • Diabetes 6-13%
It is usually develop during the second decade of life
The early lesion appears to be related more to insulin resistance
Defective insulin production occurs only in late phase of hemosiderosis
• Hypothyroidism 10-11%
It may be subclinical hypothyroidism
• Hypoparathyroidism 0-13%
It is a late complication of iron overload
Onset after age 16
Majority is having mild form of disease

36. Effect of Endocrine System on Normal Hematopoiesis.
Hematological Manifestations of Endocrine Disorders.
Endocrine Manifestations of Hematological Disorders.
Endocrine Complications Associated with Treatments of
Hematological Diseases.
Disorders that Presented by Both Hematological
and Endocrine Manifestations.

37. Why do I need to know?
• Endocrine abnormalities are a common late effect
• Pre-treatment counselling
• Post-treatment screening
• Knowledge of these side effects may allow creation of better
tolerated regimens

38. Thyroid toxicity
Hypothyroidism
-RT for treatment of lymphoma,craniospinal irradiation of ALL,TBI in
allogeneic BMT
-May be transient & resolve
-Half of cumulative risk in first 5 years
Hyperthyroidism
-Graves disease it may happen in 7% of patients post radiotherapy
-Radiation induced thyroiditis :Is mostly transient and asymptomatic

39. Thyroid carcinoma
• Increased risk observed in adults treated with RT for Hodgkin
disease
• Peak incidence of thyroid carcinoma 15-19 years post RT
• Histological types similar to that occurring in Unirradiated patients

40. Thyroid dysfunction and medical therapy
Interferon
Increase incidence autoimmune hypothyroidism, hyperthyroidism and
thyroiditis
L-asparaginase
It decrease tT3 &tT4 as a result of decrease of TBG
It decrease TSH secretion from pituitary

41. Tyrosine Kinase Inhibitors
• First is a recurrence of hypothyroidism in patients with preexisting
hypothyroidism .
• The second type of thyroid disturbance seen with TKIs is
hypothyroidism in patients with previously normal thyroid
function.
• Hypothyroidism was seen in 13%, 50%, and 22% of patients treated with
imatinib, dasatinib, or nilotinib, respectively(Kim et al.,2010)
Kim TD, Schwarz M, Nogai H, et al. Thyroid dysfunction caused by second-generation tyrosine kinase
inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia. Thyroid. 2010;20(11):1209–1214.

42. Immunomodulatory Drugs: Thalidomide/Lenalidomide
• 20% of patients who received thalidomide for multiple myeloma developed a
TSH greater than 5 mIU/L, and 7% had a TSH greater than 10 mIU/L
.Hypothyroidism mostly occurred 1–6 months after initiation of treatment
(Badros et al.,2002)
• The rates of hypothyroidism with lenalidomide have been reported to be 5%–
10% (Figaro et al.,2011)
• Badros AZ, Siegel E, Bodenner D, et al. Hypothyroidism in patients with multiple myeloma following treatment with
thalidomide. Am J Med. 2002;112(5):412–413.
• Figaro MK, Clayton W Jr, Usoh C, et al. Thyroid abnormalities in patients treated with lenalidomide for hematological
malignancies: results of a retrospective case review. Am J Hematol. 2011;86(6):467–470.

43. Gonadal dysfunction
Testis
• It is a complex process
• Damage and recovery depends on drugs and dosage
• Germ cells more sensitive than leydig cells
• Effect of RT range from oligospermia up to azospermia depends on dose of
RT
• Spontaneous recovery from remaining stem cells
• In men recovery of spermatogenesis has been described very rarely in adult
transplanted patients conditioned with fractionated TBI
• Decrease of serum testosterone is mostly transient and recovers weeks-to
months after grafting

44. OVARY
• Effect are age and dose dependent
• Older women smaller pool of oocytes ,increase incidence of POF
• Younger women frequently have normal ovarian function but premature
menopause
• Ovarian failure is the most frequent complication in women after auto-
and allo-HSCT.
• Post-transplant recovery of the ovarian function is rare and appears to be
age-dependent, occurring more frequently in young girls than in adult
women

46. Hypothalamus-Pituitary-Adrenal Axis
• Secondary adrenal insufficiency due to the suppression of the
hypothalamic-pituitary-adrenal axis is mainly related to the
duration and cumulative dose of corticosteroid treatments
received .
• that physicians be aware of the risk of AS in patients on long
term steroids can be defined as more than 3 weeks of continuous
treatment with more than 7.5 mg prednisolone, 0.75 mg
dexamethasone, or 20 mg hydrocortisone

47. • If AS is suspected, biochemical testing of the HPA axis should
be considered after GC treatment has been reduced to a
physiologic dose. present and further GC withdrawal should
occur only once testing has normalized
• The use of replacement therapy with short acting steroids is
recommended until the adrenal axis recovers with a progressive
reduction of the corticosteroid dose, to enable the adrenal axis to
gradually recover

49. Immune checkpoint inhibitors
• It is recently become a cornerstone for the treatment of different advanced
cancers.
• These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-
lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1(PD-1)
and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate
the immune system against tumor cells, but can also trigger a myriad of
autoimmune side effects, termed immune-related adverse events (irAEs).
• In particular, there are a number of endocrine-related irAEs.
• Current data from clinical trials show increased incidence of hypophysitis with
CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade.
• In addition, a few cases of type 1 diabetes mellitus and primary adrenal
insufficiency have been reported

50. Effect of Endocrine System on Normal Hematopoiesis.
Hematological Manifestations of Endocrine Disorders.
Endocrine Manifestations of Hematological Disorders.
Endocrine Complications Associated with Treatments of
Hematological Diseases.
Disorders that Presented by Both Hematological
and Endocrine Manifestations.

52. • POEMS syndrome is a rare multiorgan disorder resulting from an underlying
plasma cell dyscrasia,
• It is characterized by (P) Polyneuropathy, (O) Organomegaly
(hepatosplenomegaly or lymphadenopathy), (E) Endocrinopathy (diabetes
mellitus,hypothyroidism, or hypogonadism), (M) M-proteinemia, (S) Skin
changes (most frequently hyperpigmentation)
• Associated manifestations, including Castleman’s disease, edema (peripheral
edema, ascites, pleural effusions), thrombocytosis/erythrocytosis,a
predisposition towards thrombosis and abnormal pulmonary function tests

53. • The pathogenesis of POEMS syndrome is not fully understood, but the
overproduction of Vascular Endothelial Growth Factor (VEGF) secreted
by the plasmacytoma is thought to be responsible for the characteristic
symptoms